CA1243033A - Process for preparing 4-¬2- (dialkylamino)ethyl|isatins - Google Patents
Process for preparing 4-¬2- (dialkylamino)ethyl|isatinsInfo
- Publication number
- CA1243033A CA1243033A CA000482507A CA482507A CA1243033A CA 1243033 A CA1243033 A CA 1243033A CA 000482507 A CA000482507 A CA 000482507A CA 482507 A CA482507 A CA 482507A CA 1243033 A CA1243033 A CA 1243033A
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutically acceptable
- ethyl
- compound
- propylamino
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 125000004663 dialkyl amino group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 16
- 150000002923 oximes Chemical class 0.000 claims abstract description 9
- 125000006239 protecting group Chemical group 0.000 claims abstract description 5
- 230000005494 condensation Effects 0.000 claims abstract 2
- 238000009833 condensation Methods 0.000 claims abstract 2
- 239000002253 acid Substances 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 16
- -1 methoxyphenethyl Chemical group 0.000 claims description 13
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical group S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- FJUUXUYCECNKIP-UHFFFAOYSA-N 4-[2-(dipropylamino)ethyl]-7-hydroxy-1h-indole-2,3-dione;hydrobromide Chemical compound Br.CCCN(CCC)CCC1=CC=C(O)C2=C1C(=O)C(=O)N2 FJUUXUYCECNKIP-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- DHLUNHRJNTUEMS-UHFFFAOYSA-N 7-chloro-4-[2-(dipropylamino)ethyl]-1h-indole-2,3-dione Chemical compound CCCN(CCC)CCC1=CC=C(Cl)C2=C1C(=O)C(=O)N2 DHLUNHRJNTUEMS-UHFFFAOYSA-N 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 239000012038 nucleophile Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 5
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- VBMMNCUKXRDGAZ-UHFFFAOYSA-N 4-[2-(dipropylamino)ethyl]-1h-indole-2,3-dione Chemical group CCCN(CCC)CCC1=CC=CC2=C1C(=O)C(=O)N2 VBMMNCUKXRDGAZ-UHFFFAOYSA-N 0.000 claims 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 abstract description 12
- 239000000556 agonist Substances 0.000 abstract description 6
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 2
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 abstract description 2
- ZOUJGGOSVFONLB-UHFFFAOYSA-N 4-[2-(dipropylamino)ethyl]-4-hydroxy-1,3a-dihydroindole-2,3-dione Chemical compound CCCN(CCC)CCC1(O)C=CC=C2NC(=O)C(=O)C12 ZOUJGGOSVFONLB-UHFFFAOYSA-N 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ZNBNBTIDJSKEAM-UHFFFAOYSA-N 4-[7-hydroxy-2-[5-[5-[6-hydroxy-6-(hydroxymethyl)-3,5-dimethyloxan-2-yl]-3-methyloxolan-2-yl]-5-methyloxolan-2-yl]-2,8-dimethyl-1,10-dioxaspiro[4.5]decan-9-yl]-2-methyl-3-propanoyloxypentanoic acid Chemical compound C1C(O)C(C)C(C(C)C(OC(=O)CC)C(C)C(O)=O)OC11OC(C)(C2OC(C)(CC2)C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CC1 ZNBNBTIDJSKEAM-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000003291 dopaminomimetic effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 229910000378 hydroxylammonium sulfate Inorganic materials 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- QBHBHOSRLDPIHG-UHFFFAOYSA-N (4-hydroxy-3-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(O)C([N+]([O-])=O)=C1 QBHBHOSRLDPIHG-UHFFFAOYSA-N 0.000 description 2
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 2
- 101150049660 DRD2 gene Proteins 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 210000000748 cardiovascular system Anatomy 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
- 229960002327 chloral hydrate Drugs 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000002889 sympathetic effect Effects 0.000 description 2
- 210000002820 sympathetic nervous system Anatomy 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- QOMUPVPAASAYLX-UHFFFAOYSA-N 1h-indole-2,3-dione;hydrobromide Chemical compound Br.C1=CC=C2C(=O)C(=O)NC2=C1 QOMUPVPAASAYLX-UHFFFAOYSA-N 0.000 description 1
- OBBPMKUESGLNAB-UHFFFAOYSA-N 2-(4-hydroxy-3-nitrophenyl)-n-[2-(4-methoxyphenyl)ethyl]-n-propylacetamide Chemical compound C=1C=C(O)C([N+]([O-])=O)=CC=1CC(=O)N(CCC)CCC1=CC=C(OC)C=C1 OBBPMKUESGLNAB-UHFFFAOYSA-N 0.000 description 1
- QKPGFMWOLHVNKY-UHFFFAOYSA-N 2-(4-hydroxy-3-nitrophenyl)acetamide Chemical compound NC(=O)CC1=CC=C(O)C([N+]([O-])=O)=C1 QKPGFMWOLHVNKY-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- ACSAKRLPJQIBFB-UHFFFAOYSA-N 2-phenyl-n-(2-phenylethyl)ethanamine Chemical compound C=1C=CC=CC=1CCNCCC1=CC=CC=C1 ACSAKRLPJQIBFB-UHFFFAOYSA-N 0.000 description 1
- LJQFYBCLMVVNAQ-UHFFFAOYSA-N 3-(2-aminoethyl)aniline Chemical compound NCCC1=CC=CC(N)=C1 LJQFYBCLMVVNAQ-UHFFFAOYSA-N 0.000 description 1
- WUXCECMNMNJYSC-UHFFFAOYSA-N 37777-68-7 Chemical group OC(=O)CC1=CC=C(Cl)C([N+]([O-])=O)=C1 WUXCECMNMNJYSC-UHFFFAOYSA-N 0.000 description 1
- BGYWHGYYDCEEOX-UHFFFAOYSA-N 4-(2-aminoethyl)-1h-indole-2,3-dione Chemical compound NCCC1=CC=CC2=C1C(=O)C(=O)N2 BGYWHGYYDCEEOX-UHFFFAOYSA-N 0.000 description 1
- IQOJLILDLIAACI-UHFFFAOYSA-N 4-[2-(dimethylamino)ethyl]-7-hydroxy-1h-indole-2,3-dione;hydrobromide Chemical compound Br.CN(C)CCC1=CC=C(O)C2=C1C(=O)C(=O)N2 IQOJLILDLIAACI-UHFFFAOYSA-N 0.000 description 1
- FAZLVYBTACOVTL-UHFFFAOYSA-N 4-[2-(dipropylamino)ethyl]-1h-indole-2,3-dione;hydrochloride Chemical compound Cl.CCCN(CCC)CCC1=CC=CC2=C1C(=O)C(=O)N2 FAZLVYBTACOVTL-UHFFFAOYSA-N 0.000 description 1
- SDGBJOLIHURNOA-UHFFFAOYSA-N 4-[2-(dipropylamino)ethyl]-7-hydroxy-1h-indole-2,3-dione Chemical compound CCCN(CCC)CCC1=CC=C(O)C2=C1C(=O)C(=O)N2 SDGBJOLIHURNOA-UHFFFAOYSA-N 0.000 description 1
- LMYSNFBROWBKMB-UHFFFAOYSA-N 4-[2-(dipropylamino)ethyl]benzene-1,2-diol Chemical compound CCCN(CCC)CCC1=CC=C(O)C(O)=C1 LMYSNFBROWBKMB-UHFFFAOYSA-N 0.000 description 1
- FMWNILGNRRXNIQ-UHFFFAOYSA-N 5-[2-(dipropylamino)ethyl]-2-methoxyaniline;hydrochloride Chemical compound Cl.CCCN(CCC)CCC1=CC=C(OC)C(N)=C1 FMWNILGNRRXNIQ-UHFFFAOYSA-N 0.000 description 1
- BZWNPMVNJLJTAI-UHFFFAOYSA-N 7-hydroxy-4-[2-[2-phenylethyl(propyl)amino]ethyl]-1h-indole-2,3-dione Chemical compound C=1C=C(O)C=2NC(=O)C(=O)C=2C=1CCN(CCC)CCC1=CC=CC=C1 BZWNPMVNJLJTAI-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BLDOUNPXTAIOBV-UHFFFAOYSA-N Br.C1(=CC=CC=C1)C(CNCCC1=C2C(C(NC2=C(C=C1)O)=O)=O)C1=CC=CC=C1 Chemical compound Br.C1(=CC=CC=C1)C(CNCCC1=C2C(C(NC2=C(C=C1)O)=O)=O)C1=CC=CC=C1 BLDOUNPXTAIOBV-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 240000007711 Peperomia pellucida Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 206010047141 Vasodilatation Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000003257 anti-anginal effect Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 229910010277 boron hydride Inorganic materials 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- UXSKFQZQSMELPF-UHFFFAOYSA-N carbonic acid;methyl hydrogen sulfate Chemical compound OC(O)=O.COS(O)(=O)=O UXSKFQZQSMELPF-UHFFFAOYSA-N 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 229940000032 cardiovascular system drug Drugs 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920003086 cellulose ether Polymers 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000012380 dealkylating agent Substances 0.000 description 1
- 230000020335 dealkylation Effects 0.000 description 1
- 238000006900 dealkylation reaction Methods 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229940052760 dopamine agonists Drugs 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- FPVGTPBMTFTMRT-NSKUCRDLSA-L fast yellow Chemical compound [Na+].[Na+].C1=C(S([O-])(=O)=O)C(N)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 FPVGTPBMTFTMRT-NSKUCRDLSA-L 0.000 description 1
- IYWCBYFJFZCCGV-UHFFFAOYSA-N formamide;hydrate Chemical compound O.NC=O IYWCBYFJFZCCGV-UHFFFAOYSA-N 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000005908 glyceryl ester group Chemical group 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000002496 methyl group Chemical class [H]C([H])([H])* 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- NWKYZYGOSPOKDY-UHFFFAOYSA-N n,n-dimethylformamide;pyridine Chemical compound CN(C)C=O.C1=CC=NC=C1 NWKYZYGOSPOKDY-UHFFFAOYSA-N 0.000 description 1
- IIIRPZWDICEMGU-UHFFFAOYSA-N n-(2-phenylethyl)propan-1-amine Chemical compound CCCNCCC1=CC=CC=C1 IIIRPZWDICEMGU-UHFFFAOYSA-N 0.000 description 1
- KUKIGRQSJIATOF-UHFFFAOYSA-N n-[2-(4-methoxy-3-nitrophenyl)ethyl]-n-propylpropan-1-amine;hydrochloride Chemical compound Cl.CCCN(CCC)CCC1=CC=C(OC)C([N+]([O-])=O)=C1 KUKIGRQSJIATOF-UHFFFAOYSA-N 0.000 description 1
- CWYZDPHNAGSFQB-UHFFFAOYSA-N n-propylbutan-1-amine Chemical compound CCCCNCCC CWYZDPHNAGSFQB-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008054 sulfonate salts Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- HFFLGKNGCAIQMO-UHFFFAOYSA-N trichloroacetaldehyde Chemical compound ClC(Cl)(Cl)C=O HFFLGKNGCAIQMO-UHFFFAOYSA-N 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/38—Oxygen atoms in positions 2 and 3, e.g. isatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/616,635 US4593106A (en) | 1984-06-04 | 1984-06-04 | 4-[2-(dialkylamino)ethyl]-7-hydroxyisatins |
| US616,635 | 1984-06-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1243033A true CA1243033A (en) | 1988-10-11 |
Family
ID=24470350
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000482507A Expired CA1243033A (en) | 1984-06-04 | 1985-05-28 | Process for preparing 4-¬2- (dialkylamino)ethyl|isatins |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4593106A (enrdf_load_stackoverflow) |
| EP (1) | EP0167288A3 (enrdf_load_stackoverflow) |
| JP (1) | JPS611659A (enrdf_load_stackoverflow) |
| AU (1) | AU590516B2 (enrdf_load_stackoverflow) |
| CA (1) | CA1243033A (enrdf_load_stackoverflow) |
| DK (1) | DK240585A (enrdf_load_stackoverflow) |
| ES (1) | ES8604390A1 (enrdf_load_stackoverflow) |
| GR (1) | GR851350B (enrdf_load_stackoverflow) |
| PT (1) | PT80566B (enrdf_load_stackoverflow) |
| ZA (1) | ZA854029B (enrdf_load_stackoverflow) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL77846A (en) * | 1985-03-25 | 1989-08-15 | Warner Lambert Co | Process for the preparation of 7-amino-quinolin-4-oxy-3-carboxylic acid derivatives |
| DE3706635A1 (de) * | 1987-03-02 | 1988-09-15 | Spindler & Hoyer Kg | Verfahren zur stabilisierung der frequenz einer laserdiode unabhaengig vom diodenstrom |
| GB9300309D0 (en) * | 1993-01-08 | 1993-03-03 | Smithkline Beecham Plc | Process |
| WO2001053251A1 (fr) * | 2000-01-20 | 2001-07-26 | Sumitomo Seika Chemicals Co., Ltd. | Procede de production d'ester d'acide 3-nitro-n-(monosubstitue) aminobenzoique |
| US6743796B2 (en) | 2001-05-07 | 2004-06-01 | Wyeth | Piperazinyl-isatins |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MC1357A1 (fr) * | 1979-12-07 | 1981-08-10 | Hoffmann La Roche | Derives de 2,3-indoledione |
| US4314944A (en) * | 1980-08-22 | 1982-02-09 | Smithkline Corporation | 4-Aminoalkyl-7-hydroxy-2(3H)-indolones |
| US4414224A (en) * | 1980-08-22 | 1983-11-08 | Smithkline Beckman Corporation | Pharmaceutical composition and methods for producing dopamine agonist activity |
| EP0089394A1 (en) * | 1982-03-23 | 1983-09-28 | Sterling Drug Inc. | 1-H-Indole-2,3-dione derivatives and preparation thereof |
-
1984
- 1984-06-04 US US06/616,635 patent/US4593106A/en not_active Expired - Fee Related
-
1985
- 1985-05-28 CA CA000482507A patent/CA1243033A/en not_active Expired
- 1985-05-28 ZA ZA854029A patent/ZA854029B/xx unknown
- 1985-05-29 DK DK240585A patent/DK240585A/da unknown
- 1985-05-31 GR GR851350A patent/GR851350B/el unknown
- 1985-05-31 PT PT80566A patent/PT80566B/pt not_active IP Right Cessation
- 1985-06-03 ES ES543822A patent/ES8604390A1/es not_active Expired
- 1985-06-03 EP EP85303901A patent/EP0167288A3/en not_active Withdrawn
- 1985-06-03 JP JP60121360A patent/JPS611659A/ja active Pending
- 1985-06-04 AU AU43266/85A patent/AU590516B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| AU590516B2 (en) | 1989-11-09 |
| DK240585A (da) | 1985-12-05 |
| JPS611659A (ja) | 1986-01-07 |
| ES543822A0 (es) | 1986-01-16 |
| DK240585D0 (da) | 1985-05-29 |
| ZA854029B (en) | 1986-04-30 |
| PT80566A (en) | 1985-06-01 |
| ES8604390A1 (es) | 1986-01-16 |
| GR851350B (enrdf_load_stackoverflow) | 1985-11-25 |
| PT80566B (en) | 1987-04-09 |
| EP0167288A3 (en) | 1986-07-16 |
| EP0167288A2 (en) | 1986-01-08 |
| AU4326685A (en) | 1985-12-12 |
| US4593106A (en) | 1986-06-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4880810A (en) | Quinazolinediones and pyridopyrimidinediones | |
| US4554284A (en) | 7-(2-Aminoethyl)-1,3-benzthia- or oxa-zol-2(3H)-ones | |
| US4289772A (en) | 1-Piperidinophthalazines as cardiac stimulants | |
| US4207324A (en) | 1,2-Di-Substituted-4-haloimidazole-5-acetic acid derivatives and their use | |
| EP0046666B1 (en) | 2(3h)-indolones, process for their preparation and compositions containing them | |
| HUT77308A (hu) | Indolszármazékok és e vegyületeket tartalmazó gyógyászati készítmények | |
| US4554287A (en) | Antihypertensive 7-[2-(dialkylamino)ethyl]-4-hydroxy-1,3-benzimidazol-2-ones | |
| US3988339A (en) | Pharmaceutical compositions and methods of inhibiting phenylethanolamine N-methyltransferase | |
| CA1243033A (en) | Process for preparing 4-¬2- (dialkylamino)ethyl|isatins | |
| NO327549B1 (no) | Benzo[G]kinolinderivater for behandling av glaukom og myopi | |
| US4797403A (en) | Quinazolinediones and pyridopyrimidinediones | |
| US4767862A (en) | Substituted tetrahydro isoquinoline intermediates | |
| US4192888A (en) | Pharmaceutical compositions and method of inhibiting phenylethanolamine N-methyltransferase | |
| JPS60158170A (ja) | エテニルフェノールインドール誘導体及びそれらの塩、これらの製造方法並びにこれらを含有する薬剤 | |
| US4414224A (en) | Pharmaceutical composition and methods for producing dopamine agonist activity | |
| EP0209275B1 (en) | Benz-trisubstituted 2-aminotetralins | |
| PT794184E (pt) | Derivados de 6-metoxi-1h-benzotriazolo-5-carboxamida seus processos de producao e composicoes farmaceuticas que os contem | |
| US3966761A (en) | Novel amino-indazole compounds | |
| US4272531A (en) | 3,3'-Bis-methylene-1,3-benzo-thiazine compounds | |
| US3691176A (en) | 1-(4-fluorophenoxypropyl)-4-anilino-piperidines | |
| CA1077040A (en) | Pharmaceutically active decahydroquinoline derivatives | |
| US3517015A (en) | Tetrahydro-isoquino(2,1-d)(1,4)benzodiazepines | |
| NO781896L (no) | 4-fenyl-8-amino-tetrahydroisokinoliner, farmasoeytiske preparater som inneholder disse, fremgangsmaate til fremstilling av disse preparater og deres anvendelse som antidepresjonsmidler | |
| US4062961A (en) | Pharmaceutical compositions and methods of inhibiting phenylethanolamine N-methyltransferase | |
| US4318909A (en) | Benzoxazocines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |